Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot’s syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot’s syndrome type 1.

中文翻译：

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由于编码单核苷酸 (C)8 束的继发性体细胞突变，导致结肠癌和肝转移中 MSH6 免疫表达丧失的 1 型特科特综合征一例：病例报告。


林奇综合征（LS）被称为遗传性癌症综合征，其特征是微卫星不稳定性，表现为编码区和/或非编码区中重复序列数量的改变。 DNA 错配修复 (MMR) 蛋白（例如 MLH1、MSH2、MSH6 和 PMS2）的免疫组织化学染色 (IHC) 已被认为是筛选 LS 的有用技术。然而，先前的研究表明，即使 MMR 基因没有种系突变，由于染色模式可变，IHC 的评估也需要特别谨慎。一名 48 岁男性，曾接受间变性星形细胞瘤治疗，被转诊至我们科室，对进展性贫血进行精确检查。全身检查发现降结肠和胃有两处晚期癌症。在肝脏中也检测到了血管不足的病变。病理诊断（手术标本）为降结肠低分化腺癌，胃中分化管状腺癌，肝转移，可能来自结肠。由于该病例的特殊家族史，第二位亲属中有两例患有结肠癌，因此怀疑该病例为特科特综合征1型。 MLH1 基因密码子 618 的致病性移码突变被鉴定。免疫组织化学分析 (IHC) 表明，除脑肿瘤外，MLH1 免疫表达和 PMS2 完全丧失。尽管MSH6基因未发现移码突变，但MSH6在原发性结肠癌组织学表达呈斑片状，在肝转移部位完全缺失。胃癌（本例中是一种巧合的癌症）中的 MSH6 表达是完整的。 通过结肠癌和肝脏肿瘤的克隆 PCR 鉴定出异常 (C)8 区域，但未从胃癌中鉴定出异常 (C)8 区域。在肝转移中也检测到 MSH6 基因外显子 5 的 (C)8 束发生移码突变。该病例支持了先前文献提出的一种合理机制，即 MSH6 表达以体细胞突变方式减少，这种情况可能优先发生在结肠癌而不是 MLH1/PMS2 缺陷型 1 型特科特综合征的胃癌中。